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Landmark trials established equivalent survival regardless of extent of breast surgery in early-stage breast cancer. However, recent studies suggest a survival advantage for breast conserving surgery (BCS) with radiotherapy (BCT). This study assesses the impact of type of surgery on overall survival (OS), breast cancer specific survival (BCSS) and local recurrence (LR) in a modern population-based cohort. Female patients aged ≥18, pT1-2pN0, who had surgery between 2006 and 2016 were identified from Breast Cancer Outcome Unit prospective database. Neoadjuvant chemotherapy patients were excluded. Multivariable Cox regression was used to assess the effect of surgical procedure on OS, BCSS, and LR on cohort with complete data. BCT was performed in 8422 patients and TM in 4034 patients. The baseline characteristics differed between the groups. Mean follow up was 8.3 years. BCT was associated with increased OS HR 1.37, p < 0.001, BCSS survival HR 1.49, p < 0.001, and similar LR HR 1.00, p > 0.90. This study supports that in early-stage breast cancer, BCT has improved BCSS compared to TM without an increased risk of LR. •In the modern era of systemic therapy, breast conserving therapy improves breast cancer specific survival over mastectomy alone in patents with early-stage node negative breast cancer.•Locoregional recurrence following breast conserving therapy is low, 3.2% at a mean follow up of 8 0.3 years, and not different for patients treated with mastectomy.•10-year breast cancer specific survival is excellent at 96.3% for women treated with breast conserving therapy, and 92.7% for patients who had mastectomy alone.

IntroductionRandomized trials demonstrated equivalent survival between breast-conserving surgery combined with radiotherapy (BCT) and mastectomy alone. Contemporary retrospective studies using pathological stage have reported improved survival with BCT. However, pathological information is unknown before surgery. To mimic real-world surgical decision-making, this study assesses oncological outcomes by using clinical nodal status.MethodsFemale patients aged 18–69 years who were treated with upfront BCT or mastectomy between 2006 and 2016 for T1-3N0-3 breast cancer were identified by using prospective, provincial database. The patients were divided into clinically node-positive (cN+) and node-negative (cN0) strata. Multivariable logistic regression was used to assess the effect of local treatment type on overall survival (OS), breast cancer-specific survival (BCSS), and locoregional recurrence (LRR).ResultsOf 13,914 patients, 8228 had BCT and 5686 had mastectomy. Mastectomy patients had higher-risk clinicopathological factors: pathologically positive axillary staging was 21% in BCT and 38% in mastectomy groups. Most patients received adjuvant systemic therapy. For cN0 patients, 7743 had BCT and 4794 had mastectomy. On multivariable analysis, BCT was associated with improved OS (hazard ratio [HR] 1.37, p < 0.001) and BCSS (HR 1.32, p < 0.001), whereas LRR was not different between the groups (HR 0.84, p = 0.1). For cN+ patients, 485 had BCT and 892 had mastectomy. On multivariable analysis, BCT was associated with improved OS (HR 1.46, p = 0.002) and BCSS (HR 1.44, p = 0.008), whereas LRR was not different between the groups (HR 0.89, p = 0.7).ConclusionsIn the era of contemporary systemic therapy, BCT was associated with better survival than mastectomy, without an increased risk of locoregional recurrence for both cN0 and cN+ presentations.

Radical resection (RAMPS) of left sided pancreatic ductal adenocarcinoma (PDAC) is effective in achieving R0 margins; however, not universally accepted due to lack of improved survival. We hypothesized that only larger tumors lead to R1 in non-RAMPS procedures. A retrospective review of charts between 2008 and 2020 was performed. The primary outcome was evaluating R0 resection based on left-sided tumors’ size and location, and secondary outcomes were OS and DFS. Sixty-eight percent had R0 resection. R1 groups’ tumors were larger (5.5 cm vs. 3.8 cm, p = 0.004) and had higher LVI involvement (p = 0.003). OS and DFS did not differ on multivariate analysis. Tumor size above 4 cm in the tail was associated with R1 (p = 0.01). Larger tumors in the tail, but not body were associated with R1, but not worse survival. Perhaps larger tumors in the tail are a surrogate marker of poor disease biology. •Positive margins signify poor tumor biology.•Tumors over 4 cm in the tail are associated with positive margins.•Tumors in the body are associated with positive margins regardless of size.

This study's objective was to evaluate the utility of intraoperative frozen section (IFS) performed during parathyroidectomy for treatment of primary hyperparathyroidism (PHP), and to identify patients for whom it is most helpful. A retrospective chart review was carried out for all patients who underwent parathyroidectomy for treatment of PHP between January 2013 and June 2018. 262 patients made up the final study population. Overall, IFS provided information that influenced the operative plan in 46 patients (17.6%). IFS altered the operative plan in 10.2% of cases that were correctly preoperatively localized, and in 41.5% of cases that were either incorrectly or not preoperatively localized. IFS did not provide information that influenced the operative plan during parathyroidectomy for treatment of PHP for the majority of patients. Patients that present with normal PTH and hypercalcemia, or those who do not localize preoperatively, are most likely to benefit from IFS. •Intraoperative frozen section rarely influenced the plan during parathyroidectomy.•It altered the plan in 10.2% of cases correctly localized.•It also altered the plan in 41.5% of cases that were incorrectly or not localized.•It most likely benefits patients that present with normal PTH and hypercalcemia. This study's objective was to evaluate the utility of intraoperative frozen section (IFS) performed during parathyroidectomy for treatment of primary hyperparathyroidism, and to identify patients for whom it is most helpful. IFS did not provide information that influenced the operative plan for the majority of patients. Patients that present with normal PTH and hypercalcemia, or those who do not localize preoperatively, are most likely to benefit from IFS.

The study objective was to evaluate the intraoperative 50% decrease in PTH level ± PTH normalization for its accuracy and efficiency in predicting cure during parathyroidectomy (PTx) for the treatment of primary hyperparathyroidism (PHP). A retrospective review of patients undergoing PTx was conducted. The timepoints at which the 50% PTH decrease was reached were recorded. The accuracy of intraoperative PTH for predicting cure, defined as normocalcemia at 6 months postoperatively, was evaluated. The study population was made up of 248 PHP patients, with 247 patients achieving normocalcemia at 6 months postoperatively. If a 50% PTH decrease was used to indicate operation conclusion, 1 patient would not be cured. Persistent PTH elevation above normal range at T10 had a PPV of 77%, NPV of 99.5%, sensitivity of 95.2% and specificity of 97.3% for predicting the presence of a contralateral pathological parathyroid gland. For the study cohort, 24.5 h of cumulative operating time would be saved if the 50% PTH decrease triggered operation conclusion. A decrease in the pre-excision PTH level to 50% of the baseline level, or a decrease in the higher of the baseline or pre-excision PTH levels by 50% at 5 or 10 min post pathological parathyroid gland removal, regardless of whether the PTH level normalizes, reliably predicts cure from PHP and should be used to guide the surgeon during parathyroidectomy. •248 primary hyperparathyroid patients undergoing parathyroidectomy made up study population.•A 50% decrease in PTH, but not PTH normalization, accurately predicted cure.•A total 24.5 h of operating time would be saved if a 50% PTH decrease triggered operation conclusion.

Ability to diagnose cancer before it progresses into advanced stages is highly desirable for the best treatment outcome. A sensitive test to analyze complex samples for specific cancer biomarkers would provide with important prognostic information and help to select the best treatment regimen. A highly robust, ultra sensitive and cost-effective electronic chip platform was used to detect nucleic acid biomarkers in heterogeneous biological samples without any amplification or purification. Chronic myelogenous leukemia (CML) was chosen as a model disease due to its hallmark genetic abnormality. This disease state therefore has an ideal market to test the detection of the fusion transcripts in complex samples, such as blood. It was shown that the CML-related fusion can be detected from unpurified cell lysates and as low as 10 cells were needed for detection. Finally, patient samples were analyzed using the assay and the fusion transcripts were accurately identified in all of them.

The development of various enzyme-linked immunosorbent assays (ELISAs) coupled with surface-enhanced Raman scattering (SERS) detection is a growing area in analytical chemistry due to their potentially high sensitivity. A SERS-based ELISA with horseradish peroxidase (HRP) as an enzymatic label, an o-phenylenediamine (oPD) substrate, and a 2,3-diaminophenazine (DAP) enzymatic product was one of the first examples of such a system. However, the full capabilities of this long-known approach have yet to be revealed. The current study addresses a previously unrecognized problem of SERS detection stage performance. Using silver nanoparticles and model mixtures of oPD and DAP, the effects of the pH, the concentration of the aggregating agent, and the particle surface chloride stabilizer were extensively evaluated. At the optimal mildly acidic pH of 3, a 0.93 to 1 M citrate buffer, and AgNPs stabilized with 20 mM chloride, a two orders of magnitude advantage in the limits of detection (LODs) for SERS compared to colorimetry was demonstrated for both DAP and HRP. The resulting LOD for HRP of 0.067 pmol/L (1.3 amol per assay) underscores that the developed approach is a highly sensitive technique. We suppose that this improved detection system could become a useful tool for the development of SERS-based ELISA protocols.

Visual neglect is a common and disabling consequence of right hemisphere damage. Standard paper-and-pencil assessments may fail to detect subtle or well-compensated cases of neglect, especially under low attentional demands. This study presents and validates the Keen Eye computer-based method for diagnosing neglect using a dual-task paradigm. The method involves the simultaneous detection of lateralized visual targets and identification of centrally presented digits, increasing attentional load and sensitivity to spatial biases. We tested 102 patients with right hemisphere damage (38 with neglect, 64 without) using a predefined set of target positions that systematically varied across the visual field. Classification models based on error patterns and asymmetry coefficients demonstrated high sensitivity and specificity in distinguishing patients with neglect. The method also revealed quadrant-specific and vertically biased omissions. The findings support the utility of attention-demanding computer-based tasks for improving diagnostic precision in visual neglect and suggest potential for identifying subclinical or hidden neglect profiles.

Reactive oxygen species (ROS) are constantly generated in a living organism. An imbalance between the amount of generated reactive species in the body and their destruction leads to the development of oxidative stress. Proteins are extremely vulnerable targets for ROS molecules, which can cause oxidative modifications of amino acid residues, thus altering structure and function of intra- and extracellular proteins. The current review considers the effect of oxidation on the structural rearrangements and functional activity of hemostasis proteins: coagulation system proteins such as fibrinogen, prothrombin/thrombin, factor VII/VIIa; anticoagulant proteins – thrombomodulin and protein C; proteins of the fibrinolytic system such as plasminogen, tissue plasminogen activator and plasminogen activator inhibitor-1. Structure and function of the proteins, oxidative modifications, and their detrimental consequences resulting from the induced oxidation or oxidative stress in vivo are described. Possible effects of oxidative modifications of proteins in vitro and in vivo leading to disruption of the coagulation and fibrinolysis processes are summarized and systematized, and the possibility of a compensatory mechanism in maintaining hemostasis under oxidative stress is analyzed.